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15 - Musculoskeletal and Connective Tissue Disorders |
447
scription medication therapy should be included
in the medication history. The acetaminophen
dose from all sources, including opioid and
OTC combination products, needs to be added
together to determine safety. If the older adult
has concomitant hepatic impairment, acetamin-
ophen intake should be limited or an alternative
therapy selected. Patients should be screened
for ethanol consumption prior to recommending
chronic acetaminophen therapy, and the dose
should be decreased in anyone with regular or
excessive ethanol consumption.
46
The nonselective NSAIDs pose GI ulcer and
bleeding risks, especially in older adults.
Major
risks associated with ulcer formation are age
over 65 years; history of peptic ulcer disease
or upper GI bleeding; and concomitant medical
conditions such as cardiovascular disease,
diabetes, and renal or hepatic dysfunction.
37
Concomitant use of glucocorticoids, antiplatelet
agents, anticoagulants, tobacco, and ethanol
further increases the risk for ulcers and bleeding.
Older adults with GI ulcers secondary to NSAIDs
do not always present with the typical symp-
toms, so other assessments are required.
47
Use
of proton pump inhibitors (PPIs) with NSAIDs can
decrease GI ulcer risk but also increase therapy
cost.
21,22
H
2
-antagonists or antacids do not
adequately reduce NSAID GI ulcer risk. Refer to
Chapter 14 for a more detailed review of NSAID
risks and monitoring parameters.
Cost-effectiveness studies have indicated a
benefit using cyclooxygenase-2 (COX-2) inhibitors
in patients over age 65 years requiring NSAIDs
due to decreased GI toxicity and associated
costs. However, COX-2 inhibitors have cardio-
vascular and renal risks at least as concerning as
other NSAIDs.
37
NSAIDs can increase blood pres-
sure, worsen heart failure, precipitate renal insuf-
ficiency, and increase risk of myocardial infarc-
tion through their impact on the renal collecting
tubules, leading to increased fluid retention.
48
Opioid use has been associated with GI
adverse effects of constipation and nausea,
which can also be conditions with which older
adults are struggling.
37
Opioids can increase
cardiovascular adverse effects, pneumonia,
falls, hospitalizations, and death.
O F
Etiology, Epidemiology, and
Clinical Presentation Specic to
Older Adults
Osteoporosis is a skeletal disease characterized
by low bone density, decreased bone strength,
and deterioration of bone micro-architecture that
results in an increase in bone fragility and risk
of fracture.
Osteoporosis associated with aging
is related more to bone formation problems than
bone resorption problems, which are more asso-
ciated with bone loss due to estrogen deficiency
during and shortly after menopause.
49
The risk
factors for osteoporosis and osteoporotic frac-
tures are similar between middle-aged and older
adults
50-53
; however, some of these risks become
more prevalent in older adults. For women,
osteoporosis is generally related to estrogen
deficiency and aging, whereas for men, osteo-
porosis is usually related to secondary causes,
aging, hypogonadism, or a combination of these
risks. Some of the diseases and medications
associated with bone loss have higher preva-
lence in older adults. Risk factors for nursing
home admission after a fracture or for a subse-
quent fracture include older age, cognitive
impairment, lower bone mineral density, impaired
depth perception, impaired mobility, previous
falls, dizziness, poor or fair self-perceived health,
malnutrition, comorbidities, inadequate social
support, depression, polypharmacy, and history
of inpatient delirium.
54,55
Osteoporosis and osteoporotic fractures
increase with aging.
53,56,57
Middle-aged women
have an osteoporosis prevalence of 4%, which
increases to 44% to 52% in women 80 years and
older.
53
Whites and Hispanics have the highest
incidence of osteoporosis
58
and fractures even
after adjusting for weight, bone mineral density
(BMD), and other factors.
51-53
About 50% of
women and 30% of men will experience a frac-
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| Fundamentals of Geriatric Pharmacotherapy
ture after the age of 60, which increases risk for a
subsequent fracture.
56,59
In white women, 75% of
fractures occur after the age of 75.
53
Almost all hip
fractures are related to falling.
56,60
More fractures
occur in nursing homes than the community.
54
Hip
fracture incidence is decreasing, but even in 2010,
258,000 older adults were admitted to the hospital
for a hip fracture.
60
Although osteoporotic fractures
are more common than strokes, heart attacks, and
breast cancer combined and consume signifi-
cant healthcare dollars ($17 billion in 2005),
52
less attention is given to them. This is unfortunate
because the number of patients needed to treat to
prevent a second fracture is less than the number
of patients needed to treat to prevent a second
myocardial infarction with aspirin, statins, or beta
blockers.
57
Decreasing osteoporosis and hip frac-
tures by 10% in older women and men is included
in the Healthy People 2020 goals.
58
Fractures can be silent or painful. They can
result in decreased height, mobility, functioning,
independence, and respiratory and GI func-
tion (secondary to spine kyphosis) and death.
Complications following a hip fracture include
fear of falling, thromboembolic events, depres-
sion, infection, subsequent fracture, pressure
ulcer, poor nutrition, and death. Men,
51
older
adults (especially those with comorbidities),
57
and
nursing home residents
54
have a higher mortality
rate after fracture than women, younger adults,
and community dwelling older adults. After hip
or femur fracture surgery, 16% of patients went
home and 84% went to inpatient rehabilitation, a
long-term care hospital, or a skilled nursing facility,
with an average stay of 36 ± 41 days.
61
About 46%
of the patients used home healthcare services 6
months after the fracture. One year after the frac-
ture, 29% of the surgical patients had died and 4%
to 20% still resided in a nursing home.
50,52,61
Only
about half of the patients with a fracture returned
to pre-fracture mobility.
50,54
Summary of Standard Treatment in
General Adult Population
All older adults should be assessed for osteo-
porosis, starting with an annual height measure-
ment. Overall height loss of 1.5 inches or more or
annual loss of 0.8 inches or more are suggestive
of osteoporosis and warrant further investiga-
tion.
50
The fracture risk assessment tool (FRAX)
can be used for all men and postmenopausal
women 40–90 years old who have never taken
osteoporosis medications or who have been off
them for 1–2 years. The tool can be used for
screening, diagnosis, and treatment decisions,
and the results motivate patients to seek osteopo-
rosis therapy.
50-53,62
A limitation of FRAX is that not
all secondary causes and risks, especially pres-
ence of falls, are included.
57
The preferred osteo-
porosis diagnostic test is a central DXA (lumbar
spine, femoral neck, total hip) with vertebral
imaging sometimes recommended.
50,63
FRAX
and DXA are described in Chapter 4. Secondary
causes should be explored with specific tests
based on the condition.
50-53
Each older adult
should also receive a falls risk assessment and
be offered interventions to prevent identified
risks.
2,9,11,50
Osteoporosis prevention and treatment
requires a lifestyle that includes adequate
calcium and vitamin D intake; exercise to
improve bone strength, muscle function, and
balance; minimization of alcohol and caffeine
intake; no smoking; and fall prevention.
9,50-53,64
Calcium alone
65
does not prevent fractures.
Vitamin D alone
66
does not significantly influence
bone density. After reanalysis of past studies
and correcting meta-analyses, only combination
calcium and vitamin D therapy prevented frac-
tures in nursing home/assisted living residents.
65
Variability exists for the desired 25(OH) vitamin
D concentration, with ranges from 20 ng/mL
64
to
30 ng/mL
50
or greater
51,52
suggested as the
desired goal.
Guidelines are consistent in defining patients
requiring osteoporosis therapy.
50-53
The criteria
for prescription osteoporosis medications are
history of hip or vertebral fracture; DXA T-score
less than or equal to –2.5 at femoral neck, total
hip or spine; or low bone density (osteopenia)
defined as a T-score between –1 and –2.5 with
either the FRAX
10-year all major osteoporosis–
related fracture probability 20% or higher or the
10-year hip fracture probability 3% or higher.
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449
Guidelines assist with osteoporosis product
decisions. Table 15-2 contains specific informa-
tion about OTC and prescription medications for
osteoporosis prevention and treatment. Sequen-
tial therapy, which is a bone formation medica-
tion (i.e., teriparatide) used first followed by an
antiresorptive medication (i.e., bisphospho-
nates, denosumab, raloxifene), is advocated by
the most recent National Osteoporosis Founda-
tion (NOF) guideline
50
to treat osteoporosis and
prevent fractures
50
; but teriparatide is generally
not prescribed first because of its route of admin-
istration, cost, and lack of hip fracture preven-
tion data.
In practice, teriparatide is usually
reserved for patients with significant bone loss
(e.g., T-score less than –3.5 or fragility fracture)
or patients that cannot use or tolerate antiresorp-
tive medications.
50,51,53
The American Associa-
tion
of Clinical Endocrinologists guideline ranks
alendronate, risedronate, zoledronic acid, and
denosumab as first-line therapy.
52
Combination therapy is rarely needed.
50
Duration of therapy is not known, but limiting
therapy to 3 to 5 years in older adults with low
risk
50,52,67
and 5 to 10 years for older adults with
high risk is suggested by guidelines and expert
opinion.
52,67
Because bisphosphonates have a
long duration of action, a drug holiday of 1 (rise-
dronate), 2 (alendronate), or 3 (zoledronic acid)
years can be used with the same or a different
medication class started afterward.
52,67
When to
reinitiate therapy is unclear; however, sugges-
tions include when bone markers increase,
bone density significantly decreases, or fracture
occurs.
52,67,68
Ibandronate, raloxifene, and teriparatide are
second-line, raloxifene and teriparatide are also
third-line, and calcitonin is fourth-line therapy.
52
Although raloxifene or nasal calcitonin can be
used, these medications have not shown hip and
nonvertebral fracture prevention.
50-53,57
Raloxi-
fene is also associated with a small increased
risk for fatal strokes. Infrequently, calcitonin is
used for pain management after an acute osteo-
porotic fracture. Estrogen and bazedoxifene
therapy are not used for older women for osteo-
porosis unless all other medications cannot be
used.
69
Men at high risk for a fracture should take
an osteoporosis medication. Men with clinically
significant androgen deficiency symptoms and
low testosterone concentrations could receive
testosterone replacement therapy, if they have
no current or past prostate cancer.
51
Testos-
terone has a minor effect on bone. In older men,
testosterone therapy can increase cardiovas-
cular disease and mortality, creating concern
about testosterone use in this population.
70
An interprofessional team and a multifacto-
rial approach to preventing and treating osteo-
porosis and fractures are needed, with attention
to patient lifestyle, polypharmacy, home environ-
ment, provider and patient education, and patient
assessment.
54,59
Standards, such as the Healthy
People 2020 goals
58
and The Joint Commis-
sion standards, have been developed to ensure
patients with a fragility fracture are evaluated for
a secondary cause, have a DXA performed or
treatment initiated, and receive follow-up after
emergency department discharge.
71
Fracture
liaison teams help achieve these goals and
improve prevention of second fractures.
59
Review of Evidence Base
Supporting Treatment
Recommendations for Older Adults
All bisphosphonates are indicated for postmeno-
pausal women but only alendronate, risedronate,
and zoledronic acid have indications for male
osteoporosis. Denosumab and teriparatide are
indicated for postmenopausal women and men
at high risk for fracture. Raloxifene is indicated
for prevention and treatment of osteoporosis in
postmenopausal women and to decrease breast
cancer risk in postmenopausal women with
osteoporosis. Calcitonin is indicated in women
at least 5 years postmenopause. Zoledronic acid
is the only osteoporosis medication with an FDA
indication for secondary fracture prevention.
50,52
Some osteoporosis studies compared the older
participants to younger participants and found
no differences; but generally these comparisons
were underpowered to evaluate age differences
in bone density, fracture risk reduction, and
adverse reactions.
57
Effectiveness data in adults
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| Fundamentals of Geriatric Pharmacotherapy
Table 15-2. Pharmacotherapy for Osteoporosis Prevention and Treatment
Drug Dose Advantages Limitations
Calcium
Most common
salts used
are carbonate
(40% elemental
calcium) and
citrate (21%
elemental
calcium)
300–500 mg
elemental calcium
tablets as needed
to achieve
adequate intake
of 1,000 mg for
men 50–70 years
old and 1,200 mg
daily for women
50 years and
older and men 71
years and older.
Maximum intake
from food and
supplements per
IOM is 2,000 mg
per day
64
but per
NOF guideline
is 1,500 mg per
day.
50
Sometimes
easier than
ingesting
foods,
especially for
those who
are lactose
intolerant
or have
dyslipidemia.
Alternative
formulations–
chewable,
dissolving
tablet, liquid.
Administration
Dietary intake preferred.
Carbonate but not citrate products should
be taken with food.
Citrate tablets are more expensive and
more tablets might be needed.
Adverse effects
Constipation, gas, bloating, kidney stones
(rare).
Slight increase in myocardial infarcts and
kidney stones with daily calcium use
greater than adequate intakes.
Drug interactions
Proton pump inhibitors, iron, tetracycline,
quinolones, bisphosphonates, phenytoin,
and fluoride.
Food interactions
Oxalates, phytates, sulfates, and fiber
(variable).
Vitamin D 600–1000 units
one or two times
per day to achieve
therapeutic
25 (OH) vitamin D
concentration
(>22–30 ng/mL).
Higher daily doses
or 50,000 units
weekly to monthly
sometimes used
for insufficiency
until replete.
50,000 units 1–2
times weekly for
8–12 weeks used
for deficienc
y until
replete.
More accessible
than vitamin
D–fortified
foods.
Administration
Severe renal or hepatic failure, use different
vitamin D analogs.
Obesity or malabsorption conditions—
potentially need higher dose.
Adverse effects
Hypercalcemia (uncommon).
Drug interactions
Phenytoin, barbiturates, carbamazepine,
rifampin, cholestyramine, colestipol,
orlistat, and mineral oil.
Monitoring
25(OH) vitamin D concentration; after 3
months to assess drug therapy.
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451
Bisphosphonates
•
Alendronate
•
Ibandronate
•
Risedronate
•
Zoledronic
acid
10 mg daily;
70-mg tablet,
70-mg tablet
with vitamin D
(2,800 or 5,600
units), or 70-mg
effervescent
tablet weekly.
150 mg monthly,
3-mg intravenous
infusion over
15–30 seconds
quarterly.
5 mg daily, 35 mg
weekly, 150 mg
monthly.
35 mg delayed-
release tablet.
5 mg intravenous
infusion over 15
minutes yearly
for treatment and
every 2 years for
prevention.
Reasonably safe,
7–10-year
safety data.
Much BMD
data. Spine
and hip (except
ibandronate)
fracture
prevention
data. Weekly,
monthly,
quarterly,
and yearly
administration
sometimes
improves
adherence.
Administration
Check Medicare Part D plan to see what is
Tier 1 and requirements for intravenous
administrations.
Normal serum calcium and creatinine
required before intravenous therapy.
Complex oral administration
Take with a full glass of water not juice,
coffee, or tea and on an empty stomach.
Remain upright for at least 30–60 minutes.
Do not take with any other medications.
Special products
Effervescent alendronate:
Dissolve tablet in 4 oz plain water; wait 5
minutes for effervescence to stop, stir for
10 seconds, and then ingest 30 minutes
before breakfast; other directions the
same.
Delayed-release risedronate:
Immediately after breakfast with 4 oz plain
water; other directions the same.
Missed doses
If weekly, take next day; need ≥5 days
between doses.
If monthly, take as soon as remembered;
need ≥7 days between doses.
Contraindications
Renal function CrCl <30–35 mL/min
(controversial); if age-related renal
dysfunction might be ok to use oral
therapy. Absolute contraindication if CrCl
<30–35 mL/min or acute kidney failure for
zoledronic acid.
Esophageal disorders or severe GI problems
(oral).
Adverse effects
GI: nausea, heartburn, abdominal pain,
irritation.
Muscle aches and pains (uncommon);
discontinue if severe.
Transient (24–72 hr) flu-like symptoms with
intravenous administration, can pretreat,
sometimes decrease with subsequent
treatments.
Ulceration, perforation, and bleeding with
oral therapy (rare).
Osteonecrosis of the jaw and atypical
fractures (rare).
Drug interactions
Calcium, minerals, proton pump inhibitors,
H
2
blockers, warfarin with delayed-release
risedronate.
Table 15-2. Pharmacotherapy for Osteoporosis Prevention and Treatment (cont’d)
Drug Dose Advantages Limitations
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| Fundamentals of Geriatric Pharmacotherapy
Denosumab 60 mg
subcutaneous
injection every
6 months.
Can use in
pa
tients
with CrCl
<30 mL/min.
Administration
By healthcare provider.
Prior authorization required.
Normal serum calcium required before
therapy.
Expensive.
Adverse effects
Dermatitis, rash/eczema, bone/muscle pain,
mild GI events, cystitis, other infections,
hypocalcemia, flatulence.
Osteonecrosis of the jaw and atypical
fractures (rare).
Raloxifene 60 mg daily. Estrogen-
positive
breast cancer
prevention
indication in
women at
high risk for
fracture.
Small lipid
lowering effect.
Efficacy
Only vertebral fracture prevention.
Contraindications
Previous venous thromboembolic event.
Adverse effects
Hot flushes, leg cramps, myalgias,
thromboembolism, pulmonary embolism,
peripheral edema; cataracts and
gallbladder disease (rare).
Box warning for fatal stroke.
Calcitonin 200 units intranasal
daily, alternating
nares every other
day.
Some analgesic
effect after
a fracture.
Also used for
metastatic
bone pain.
Efficacy
Only vertebral fracture prevention.
Administration
Refrigeration until first use.
Adverse effects
Rhinitis, epistaxis, nasal irritation and dryness.
Under review for potential increased cancer risk.
Teriparatide 20 mcg
subcutaneously
daily for up to
2 years.
Only product
that builds new
bone.
Pen device for
administration.
Efficacy
Limited use for 24 months.
Might need prior authorization.
Administration
Daily injection.
Discard pen 28 days after being opened.
Refrigeration required, can complicate travel.
Expensive.
Might need prior authorization.
Contraindications
Bone cancer, Paget disease, open epiphyses,
hypercalciuria, unexplained increased
alkaline phosphatase, prior skeletal radiation.
Box warning: do not use if at risk for
osteosarcoma.
Adverse effects
Pain at injection site, headaches, nausea,
dizziness, leg cramps, arthralgias,
transient hypercalcemia, and increase in
uric acid (rare).
CrCl, creatinine clearance; IOM, Institute of Medicine; NOF, National Osteoporosis Foundation.
Table 15-2. Pharmacotherapy for Osteoporosis Prevention and Treatment (cont’d)
Drug Dose Advantages Limitations
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453
75 years and older are limited but suggestive
of vertebral fracture reduction with risedronate,
alendronate, and teriparatide and nonvertebral
and hip fracture reduction with risedronate for
those 70–79 years old.
57,72
Healthcare use and costs for treating frac-
tures are higher in older adults
73
and quality of
life
57
is reduced after a fracture, making preven-
tion important. Treating osteoporosis in older
adults is cost effective. A well-designed phar-
macoeconomic study showed that treating older
adult women 65–84 years old with osteoporosis
was cost effective and would even generate cost
savings for adults 85 years and older with osteo-
porosis.
74,75
Cost effectiveness could be realized
for men 65 years and older with a prior fracture
and men 80–85 years old with osteoporosis.
76
If
osteoporosis treatment is less than $500 annually
(2007 dollars), treating men 70 years and older
with osteoporosis would also be cost effective.
Common Problems Encountered
When Treating Older Adult Patients
with is Condition
The main challenge is to get providers to assess
and treat older adults for osteoporosis. Over a
7-year period, only 31% of older white women,
15% of older African American women, and 5%
of older men had a DXA test.
57
In the nursing
home, FRAX
overestimates the need for therapy
(81% using femoral neck T-score). If previous
fracture and/or DXA T-score are used, 54% would
need osteoporosis therapy, increasing to 73% if
vertebral imaging also is used.
77
Even after a hip
fracture, less than 22% of older adults received
a DXA or prescription therapy.
57
Osteoporosis
medication therapy use after a fracture varies by
fracture site; wrist (14%), hip (26%), and spine
(42%) with older age not influencing treatment.
78
Older adults after a fracture should be
offered osteoporosis prevention and treatment
therapies to enhance the remainder of life. Frac-
ture prevention begins within 6 to 12 months
of therapy for vertebral fracture prevention
and 18 to 24 months for hip fracture preven-
tion. Because the average life expectancies for
older adults who are 75 years or older, nursing
home residents, and assisted living residents
is greater than the onset of fracture preven-
tion,
osteoporosis medications can be consid-
ered for these populations.
57,77
However, some
comorbidities such as a neurologically limiting
stroke, advanced stage dementia, and terminal
cancer generally warrant not using osteoporosis
medications. Osteoporosis medications can be
considered for discontinuation in some patients,
especially for those patients receiving hospice
care.
Patient analysis of dietary calcium intake is
needed to determine safe calcium supplemen-
tation amount.
50
Supplementation need is the
difference between Institute of Medicine (IOM)–
recommended intakes and dietary daily calcium
ingestion. If daily calcium ingestion cannot be
determined, the National Health and Nutrition
Examination Survey average calcium intakes can
be used instead, which for women is approxi-
mately 600–640 mg elemental calcium and for
men is approximately 730–760 mg.
79
Supple-
mental doses should be distributed throughout
the day. Calcium supplement labels can be
confusing, and some older adults will need
assistance determining the calcium content of a
tablet, the number needed per day, and correct
use.
Calcium absorption is variable and likely
lower in some older adults. Calcium carbonate
but not calcium citrate requires an acid environ-
ment, which can be decreased in older adults,
for disintegration and dissolution. Taking calcium
carbonate with food might overcome this
problem. PPI use was associated with increased
fracture risk, potentially related to decreased
calcium absorption from calcium carbonate
products secondary to PPI decreased gastric
acid.
80
For older adults using PPIs, increasing
calcium carbonate daily intake and taking it
later in the day with food or using calcium citrate
might solve this absorption problem.
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Because of minimal sun exposure (residen-
tial living, sunscreen use, northern hemisphere
residence), few vitamin D–supplemented foods
and beverages, and kidney and liver age-
related changes, older adults are at increased
risk for low vitamin D concentrations or altered
metabolism. Therefore, older adults usually
need supplementation.
50-53
Based on Markov
decision analysis, universal vitamin D supple-
mentation was similar in cost effectiveness to
population screening for women and men 65
years old, but population screening for women
and men 80 years old was more cost effective
than universal supplementation.
81
Although
the IOM-recommended adequate vitamin D
intake has been increased,
64
one Canadian
study documented that a vitamin D intake of
1,000 units per day only placed 35% of older
adults in the therapeutic range (≥30 ng/mL),
whereas 4,000 units per day put 88% in the
therapeutic range.
69
Because 25(OH) vitamin D
levels are expensive, a cost-saving measure is
to draw a 25(OH) vitamin D level after taking
800–1,000 units vitamin D
3
supplement daily
for 3–4 months (time for biological steady
state) to ascertain the need for replenishment
therapy or a higher maintenance dose. Inter-
assay variability exists, so patients should have
follow-up vitamin D levels analyzed at the same
laboratories until all assays are standardized.
Various repletion dosage schedules for vitamin
D insufficiency (21–29 ng/mL) exist, ranging
from 800–4,000 units vitamin D
3
daily to 50,000
units vitamin D
2
or D
3
weekly to monthly, with
daily dosing preferred over larger, less frequent
dosing options.
For vitamin D deficiency
(<21 ng/mL), repletion dosage schedules
are also variable but generally involve using
50,000 units vitamin D
2
or D
3
1–2 times weekly
for 8–12 weeks and then implementing a daily
maintenance dose of 800–1,000 units or higher,
as needed.
50
Prior to initiating bisphosphonate therapy,
especially intravenous therapy, a patient’s serum
calcium should be in the normal range and,
if not, corrected before administration. Oral
bisphosphonates require the older adult to be
able to remain upright (seated or standing) for
at least 0.5–1 hour after ingestion, which might
be difficult for some older adults with stroke,
immobility, or dementia. For patients with diffi-
culties swallowing or with feeding tubes, effer-
vescent alendronate could be used. If the older
adult cannot tolerate oral bisphosphonates,
intravenous zoledronic acid or injectable deno-
sumab or teriparatide therapy can be insti-
tuted. With correct usage, bisphosphonates
have few adverse effects. Weekly and monthly
bisphosphonate oral administrations decrease
serious but not common GI bisphosphonate
adverse effects compared to daily use. Although
oral bisphosphonates are labeled not to use if
creatinine clearance is <30–35 mL/min, some
but not all experts suggest bisphosphonates
for 3 years for chronic kidney disease (CKD) 4
and half the dose for 3 years for CKD 5 if the
patient has age-induced renal compromise and
has had a fragility fracture suspected from high
bone turnover (e.g., from bone biopsy).
82
These
older adults should be assessed first for normal
calcium and vitamin D concentrations, and low
concentrations should be corrected before
initiating the oral bisphosphonate (this recom-
mendation is not evidence based). Intravenous
zoledronic acid is contraindicated for creatinine
clearances <35 mL/min and with acute renal
failure.
Denosumab requires a normal serum
calcium concentration before use and prior
authorization to determine insurance coverage.
A healthcare provider needs to administer deno-
sumab every 6 months, which can create trans-
portation issues for product pickup at a phar-
macy and a clinic administration visit; however,
some pharmacies are beginning to offer admin-
istration service.
Adherence (30% to 50%) and persis-
tence (30% to 35%) with osteoporosis medica-
tions are suboptimal, resulting in decreased
medication benefits.
83,84
Older adults have
circumstances that lead to decreased adher-
ence, such as increased pill burden, cogni-
tive impairment, or limited resources. Complex
product administration influences adherence;
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15 - Musculoskeletal and Connective Tissue Disorders |
455
with new and refilled prescriptions, adherence
might be corrected with the teach-back patient
education method. Patient counseling might
overcome adherence problems related to fears
about adverse effects, misunderstandings
about disease severity and medication, and
attitudes toward medications.
84
Monthly medi-
cations do not always improve persistence.
83
Intravenous and injectable therapies might
present cost issues to older adults, especially
if they are at or near the coverage gap of their
Medicare Part D insurance programs.
Due to polypharmacy, older adults are at
increased risk for medication-induced bone
loss.
85
Glucocorticoids are the most potent
bone destroying medications.
86
Although use is
limited today, they were common therapies in the
past before safer medications existed for such
morbidities as chronic obstructive pulmonary
disease and rheumatoid arthritis (RA), thereby
warranting a good past medication history
assessment. For patients starting or receiving
glucocorticoid therapy (e.g., ≥5 mg predni-
sone or equivalent for ≥3 months), a baseline
and follow-up hip and spine DXA and vertebral
imaging are recommended.
50,63
The first step of
therapy is to try to eliminate glucocorticoid use
or, if not possible, use the safest medications
with the lowest dose for the shortest duration. A
bone-healthy lifestyle and higher calcium (1,200–
1,500 mg) and vitamin D (800 units or more to
achieve therapeutic concentrations) intakes are
required if on glucocorticoids.
Although guidelines exist for glucocorticoid-
induced osteoporosis prevention and treatment,
they are frequently not followed.
87
If the FRAX
major osteoporosis fracture risk score is >20%
(high risk), then alendronate, risedronate, or
zoledronic acid can be used. Teriparatide is also
an option if the dose is 5 mg or more of pred-
nisone (or equivalent) daily or any prednisone
dose if for greater than 1 month. If the older adult
is at medium risk for osteoporosis (FRAX risk
score 10% to 20%) and the prednisone dose is
<7.5 mg daily, then alendronate or risedronate is
used, with zoledronic acid also an option if pred-
nisone 7.5 mg or more daily. For older adults at
low risk (FRAX <10%) and prednisone <7.5 mg
daily, no prescription therapy is required, but
if the dose is ≥7.5 mg or more daily, then alen-
dronate, risedronate, or zoledronic acid can be
used. Since the guideline was published, deno-
sumab has been approved and has shown some
efficacy to decrease glucocorticoid-induced
bone loss.
86
Besides glucocorticoids, many other medi-
cations have bone effects. As older adults
age, their levothyroxine dosage requirements
frequently decrease, creating excess concen-
trations that can increase bone loss if dosage
adjustments are not made. Thus, yearly
thyroxine-stimulating hormone (TSH) levels
should be drawn, with thyroid replacement
doses adjusted to achieve TSH concentra-
tions in the middle to upper normal therapeutic
range.
88
Anticonvulsant therapy with medica-
tions such as phenytoin and phenobarbital can
cause both osteoporosis and osteomalacia.
85
With long-term use of these medications, moni-
toring 25(OH) vitamin D concentrations might
be helpful to identify and correct any vitamin
D deficits. Some cancers and chemothera-
pies such as prostate and breast cancers and
gonadotropin-releasing hormone agonists (e.g.,
goserelin, leuprolide) and aromatase inhibi-
tors (e.g., anastrozole) increase bone loss and
osteoporosis.
85,89
Zoledronic acid and deno-
sumab can limit this bone loss, reduce skeletal
complications, and inhibit cancer cells. Selec-
tive serotonin reuptake inhibitors have been
associated with decreased osteoblast function
and increased fracture risk, warranting moni-
toring for falls and osteoporosis.
50,85
KEY POINT:
Most patients receiving
medications causing bone loss and fractures
have not been educated about drug-induced
osteoporosis, making additional diagnostic,
prevention, treatment, patient education,
and motivational strategies necessary.
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456
| Fundamentals of Geriatric Pharmacotherapy
R A
Etiology, Epidemiology, and
Clinical Presentation Specic to
Older Adults
RA is a progressive autoimmune disorder of
unknown etiology. It is a chronic, destructive
disease characterized by symmetric, erosive
synovitis. Up to one-third of cases are diag-
nosed at age 60 or beyond, known as elder-
onset rheumatoid arthritis (EORA).
90
Compared
to young-onset rheumatoid arthritis (YORA),
patients with EORA might have genetic differ-
ences, in particular a decreased frequency of
DRB1*04 alleles.
RA is found in approximately 0.5% to 1%
of the population impacting roughly 1.3 million
Americans.
91,92
About 2% of people 60 years and
older have RA.
90
In working-age adults, the inci-
dence is higher in women. After age 65 years,
men and women have RA at about the same
rate, but evidence in recent years suggests an
increase for women.
91
It can occur at any age
but most commonly presents in the 30s to the
50s. RA is sometimes diagnosed after age 65
years. The average age of those living with it
has gradually increased to 66.8 years, based
on 1995 data.
92
The mortality rate of people
with RA has remained relatively stable between
1965 and 2005, whereas the mortality rate overall
has declined.
93
As available treatments advance
and are able to better limit disease activity, the
psychological and physical impact of RA is
decreasing.
94
The diagnostic RA criteria
are based on
number and size of affected joints, rheuma-
toid factor and anti–cyclic citrullinated peptide
antibodies (ACPA) status, duration, and inflam-
matory laboratory parameters.
95
Presence of
these factors is entered into a weighted scoring
mechanism. A score of 6 or greater is indicative
of “definite” RA in a patient with clinical synovitis
with no other apparent etiology. RA affects both
joints and other organ systems. Joint destruction
can significantly impact daily function. Fatigue is
a component that can further limit daily function.
Other constitutional symptoms include malaise,
fever, weight loss, depression, and weakness.
96
Extra-articular manifestations of RA include
cardiovascular disease, anemia, interstitial lung
disease, osteopenia, osteoporosis, and ocular
involvement (including scleritis), rheumatoid
nodules, vasculitis, Felty syndrome, and Sjögren
syndrome. The presence of extra-articular mani-
festations and markers of more active disease
such as more involved joints, higher erythrocyte
sedimentation rate (ESR), positive rheumatoid
factors, and more functional impairment are all
associated with higher mortality rates.
91,92
The EORA patients are more likely to have
an abrupt onset with involvement of large joints
such as hip and shoulder and more frequently
present with constitutional symptoms. EORA
patients who are seropositive tend to have a
more aggressive form and require more aggres-
sive therapy, similar to their YORA counterparts.
Seronegative patients often have a disease
course that mimics or coincides with Sjögren
syndrome or polymyalgia rheumatica (PMR).
These are often easier to manage with disease
modifying anti-rheumatic drugs (DMARDs) and
glucocorticoids, and this population has a higher
rate of remission. EORA is a predictor of cardio-
vascular mortality, so aggressive cardiovascular
risk reduction and management are warranted.
90
Summary of Standard Treatment in
General Adult Population
Nonpharmacologic therapy is a key part of RA
care. Exercise to maintain ROM and strength,
rest, thermal modalities, weight loss, relaxation
techniques, and physical and occupational
therapy are all important nonpharmacologic
therapy components. Therapists can aid people
with RA in the use of joint braces and assistive
devices to minimize functional limitations.
The 2012 ACR guideline provides detailed
algorithms for RA treatment.
97
DMARD mono-
therapy is recommended in early RA without
poor prognostic factors. Early or established RA,
features of poor prognosis, and higher disease
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